tbuckley/cabot-search huggingface dataset:
Covid-19 vaccination in pregnancy
Authors: Martina L Badell, Carolynn M Dude, Sonja A Rasmussen, Denise J Jamieson
Journal: BMJ (2022)

ABSTRACT Pregnancy is an independent risk factor for severe covid-19. Vaccination is the best way to reduce the risk for SARS-CoV-2 infection and limit its morbidity and mortality. The current recommendations from the World Health Organization, Centers for Disease Control and Prevention, and professional organizations are for pregnant, postpartum, and lactating women to receive covid-19 vaccination. Pregnancy specific considerations involve potential effects of vaccination on fetal development, placental transfer of antibodies, and safety of maternal vaccination. Although pregnancy was an exclusion criterion in initial clinical trials of covid-19 vaccines, observational data have been rapidly accumulating and thus far confirm that the benefits of vaccination outweigh the potential risks. This review examines the evidence supporting the effectiveness, immunogenicity, placental transfer, side effects, and perinatal outcomes of maternal covid-19 vaccination. Additionally, it describes factors associated with vaccine hesitancy in pregnancy. Overall, studies monitoring people who have received covid-19 vaccines during pregnancy have not identified any pregnancy specific safety concerns. Additional information on non-mRNA vaccines, vaccination early in pregnancy, and longer term outcomes in infants are needed. To collect this information, vaccination during pregnancy must be prioritized in vaccine research.
Cis interactions between CD2 and its ligands on T cells are required for T cell activation
Authors: Bin Li, Yan Lu, Ming-Chao Zhong, Jin Qian, Rui Li, Dominique Davidson, Zhenghai Tang, Kaiwen Zhu, Jérémy Argenty, Anne Gonzalez de Peredo, Bernard Malissen, Romain Roncagalli, André Veillette
Journal: Science Immunology (2022)

CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs. Rather, CD48 was also needed on T cells. One exception was during cytotoxicity, which required CD48 on T cells and APCs. Fluorescence resonance energy transfer (FRET) studies in nonimmune cells provided evidence that cis interactions between CD2 and CD48 existed within individual cells. CD2-CD48 interactions on T cells enabled more robust T cell receptor (TCR) signals, including protein tyrosine phosphorylation. Using T cells from a CD2 knock-in mouse in which a tag was inserted at the carboxyl terminus of CD2, mass spectrometry analyses revealed that the role of CD2 in T cell activation correlated with its ability to interact with components of the TCR complex and the protein tyrosine kinase Lck. CD2-CD58 provided a similar function in human T cells. Thus, our data imply that T cell-intrinsic cis interactions of CD2 with its ligands are required for TCR signaling and T cell activation. Interactions with ligands on APCs contribute during cytotoxicity.
The past, present, and future of antibiotics
Authors: Michael A. Cook, Gerard D. Wright
Journal: Science Translational Medicine (2022)

Antibiotics have transformed modern medicine. They are essential for treating infectious diseases and enable vital therapies and procedures. However, despite this success, their continued use in the 21st century is imperiled by two orthogonal challenges. The first is that the microbes targeted by these drugs evolve resistance to them over time. The second is that antibiotic discovery and development are no longer cost-effective using traditional reimbursement models. Consequently, there are a dwindling number of companies and laboratories dedicated to delivering new antibiotics, resulting in an anemic pipeline that threatens our control of infections. The future of antibiotics requires innovation in a field that has relied on highly traditional methods of discovery and development. This will require substantial changes in policy, quantitative understanding of the societal value of these drugs, and investment in alternatives to traditional antibiotics. These include narrow-spectrum drugs, bacteriophage, monoclonal antibodies, and vaccines, coupled with highly effective diagnostics. Addressing the antibiotic crisis to meet our future needs requires considerable investment in both research and development, along with ensuring a viable marketplace that encourages innovation. This review explores the past, present, and future of antimicrobial therapy.
Underrecognition of Symptoms During Breast Radiotherapy
Authors: Katie Fitzgerald Jones, Lakeshia Cousin, Salimah H. Meghani
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Biologics and airway remodeling in severe asthma
Authors: Gilda Varricchi, Sebastian Ferri, Jack Pepys, Remo Poto, Giuseppe Spadaro, Emanuele Nappi, Giovanni Paoletti, Johann Christian Virchow, Enrico Heffler, Walter G. Canonica
Journal: Allergy (2022)

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.
<i>LINE-1</i> RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes
Authors: Francesco Della Valle, Pradeep Reddy, Mako Yamamoto, Peng Liu, Alfonso Saera-Vila, Dalila Bensaddek, Huoming Zhang, Javier Prieto Martinez, Leila Abassi, Mirko Celii, Alejandro Ocampo, Estrella Nuñez Delicado, Arianna Mangiavacchi, Riccardo Aiese Cigliano, Concepcion Rodriguez Esteban, Steve Horvath, Juan Carlos Izpisua Belmonte, Valerio Orlando
Journal: Science Translational Medicine (2022)

Constitutive heterochromatin is responsible for genome repression of DNA enriched in repetitive sequences, telomeres, and centromeres. During physiological and pathological premature aging, heterochromatin homeostasis is profoundly compromised. Here, we showed that LINE-1 ( Long Interspersed Nuclear Element-1; L1 ) RNA accumulation was an early event in both typical and atypical human progeroid syndromes. L1 RNA negatively regulated the enzymatic activity of the histone-lysine N -methyltransferase SUV39H1 (suppression of variegation 3-9 homolog 1), resulting in heterochromatin loss and onset of senescent phenotypes in vitro. Depletion of L1 RNA in dermal fibroblast cells from patients with different progeroid syndromes using specific antisense oligonucleotides (ASOs) restored heterochromatin histone 3 lysine 9 and histone 3 lysine 27 trimethylation marks, reversed DNA methylation age, and counteracted the expression of senescence-associated secretory phenotype genes such as p16 , p21 , activating transcription factor 3 ( ATF3 ), matrix metallopeptidase 13 ( MMP13 ), interleukin 1a ( IL1a ), BTG anti-proliferation factor 2 ( BTG2 ), and growth arrest and DNA damage inducible beta ( GADD45b ). Moreover, systemic delivery of ASOs rescued the histophysiology of tissues and increased the life span of a Hutchinson-Gilford progeria syndrome mouse model. Transcriptional profiling of human and mouse samples after L1 RNA depletion demonstrated that pathways associated with nuclear chromatin organization, cell proliferation, and transcription regulation were enriched. Similarly, pathways associated with aging, inflammatory response, innate immune response, and DNA damage were down-regulated. Our results highlight the role of L1 RNA in heterochromatin homeostasis in progeroid syndromes and identify a possible therapeutic approach to treat premature aging and related syndromes.
Association of Low Emotional and Tangible Support With Risk of Dementia Among Adults 60 Years and Older in South Korea
Authors: Dae Jong Oh, Hee Won Yang, Tae Hui Kim, Kyung Phil Kwak, Bong Jo Kim, Shin Gyeom Kim, Jeong Lan Kim, Seok Woo Moon, Joon Hyuk Park, Seung-Ho Ryu, Jong Chul Youn, Dong Young Lee, Dong Woo Lee, Seok Bum Lee, Jung Jae Lee, Jin Hyeong Jhoo, Jong Bin Bae, Ji Won Han, Ki Woong Kim
Journal: JAMA Network Open (2022)

Importance The association between social support and dementia risk has been debated. Most previous prospective studies have not differentiated the subtypes of social support. Objective To examine whether the association between social support and risk of dementia differs by subtype of social support and by sex. Design, Setting, and Participants This nationwide prospective cohort study included randomly sampled South Korean adults 60 years or older. The study was launched November 1, 2010, with follow-up every 2 years until November 30, 2020. The 5852 participants who completed the assessment for social support and were not diagnosed as having dementia, severe psychiatric disorders including major depressive disorder, or major neurological disorders at the baseline assessment were included in the analysis. Exposures Geriatric psychiatrists administered the structured diagnostic interviews and physical examinations to every participant based on the Korean version of the Consortium to Establish a Registry for Alzheimer Disease (CERAD-K) Assessment Packet Clinical Assessment Battery. Main Outcomes and Measures Baseline levels of emotional and tangible support using the Medical Outcomes Survey Social Support Survey. Results Among the 5852 participants (mean [SD] age, 69.8 [6.6] years; 3315 women [56.6%]; mean [SD] follow-up duration, 5.9 [2.4] years), 237 (4.0%) had incident all-cause dementia and 160 (2.7%) had incident Alzheimer disease (AD) subtype of dementia. Compared with women who reported having emotional support, those with low emotional support had almost a 2-fold higher incidence of all-cause dementia (18.4 [95% CI, 13.6-23.2] vs 10.7 [95% CI, 9.0-12.5] per 1000 person-years) and AD (14.4 [95% CI, 10.2-18.6] vs 7.8 [95% CI, 6.3-9.3] per 1000 person-years). Adjusted Cox proportional hazard analysis revealed that low emotional support was associated with increased risk of all-cause dementia (hazard ratio, 1.61 [95% CI, 1.10-2.36]; P = .02) and AD (hazard ratio, 1.66 [95% CI, 1.07-2.57]; P = .02) only in women. Low tangible support was not associated with a risk of all-cause dementia or AD regardless of sex. Conclusions and Relevance The findings of this cohort study suggest that older women with low emotional support constitute a population at risk for dementia. The level of emotional support should be included in risk assessments of dementia.
Nonnormative Eating Behaviors and Eating Disorders and Their Associations With Weight Loss and Quality of Life During 6 Years Following Obesity Surgery
Authors: Anja Hilbert, Christian Staerk, Annika Strömer, Thomas Mansfeld, Johannes Sander, Florian Seyfried, Stefan Kaiser, Arne Dietrich, Andreas Mayr
Journal: JAMA Network Open (2022)

Importance Individuals with severe obesity presenting for obesity surgery (OS) frequently show nonnormative eating behaviors (NEBs) and eating disorders (EDs), but the long-term course and prospective associations with weight loss and health-related quality of life (HRQOL) remain unclear. Objective To examine the prevalence and prospective relevance of presurgical and postsurgical NEBs and EDs according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition , diagnosed through clinical interview, for weight loss and HRQOL up to 6 years following OS. Design, Setting, and Participants In the prospective, multicenter Psychosocial Registry for Obesity Surgery cohort study, patients seeking OS were recruited at 6 OS centers in Germany and assessed at baseline before surgery and at 6 months and 1 to 6 years after surgery. From a consecutive sample of 1040 volunteers with planned OS from March 1, 2012, to December 31, 2020, a total of 748 (71.92%) were included in this study. Across follow-up, 93 of the 748 patients (12.43%) dropped out. Data were analyzed from April to November 2021. Interventions Laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy. Main Outcomes and Measures Both NEBs and EDs were identified using the Eating Disorder Examination interview. Main outcomes were the percentage of total body weight loss (%TBWL) and HRQOL (Impact of Weight on Quality of Life-Lite; range, 0-100, with 0 indicating worst and 100 indicating best). Results In 748 patients undergoing OS (mean [SD] age, 46.26 [11.44] years; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 48.38 [8.09]; 513 [68.58%] female), the mean (SD) %TBWL was 26.70% (9.61%), and the mean (SD) HRQOL improvement was 35.41 (20.63) percentage points across follow-up. Both NEBs and EDs were common before surgery, with postsurgical improvements of varying degrees. Whereas NEBs and EDs did not reveal significant prospective associations with %TBWL, loss-of-control eating at follow-up was concurrently associated with lower %TBWL (estimate, −0.09; 95% CI, −0.14 to −0.04). Loss-of-control eating (estimate, −0.10; 95% CI, −0.17 to −0.03 percentage points) and binge-eating disorder of low frequency and/or limited duration (estimate, −6.51; 95% CI, −12.69 to −0.34 percentage points) at follow-up showed significant prospective associations with lower HRQOL. Conclusions and Relevance This cohort study found prospective relevance of loss-of-control eating and binge-eating disorder of low frequency and/or limited duration for reduced long-term HRQOL following OS. These findings underline the importance of monitoring both NEBs, especially loss-of-control eating, and EDs in the long term postsurgically to identify patients in need of targeted prevention or psychotherapy.
Precise reconstruction of the TME using bulk RNA-seq and a machine learning algorithm trained on artificial transcriptomes
Authors: Aleksandr Zaitsev, Maksim Chelushkin, Daniiar Dyikanov, Ilya Cheremushkin, Boris Shpak, Krystle Nomie, Vladimir Zyrin, Ekaterina Nuzhdina, Yaroslav Lozinsky, Anastasia Zotova, Sandrine Degryse, Nikita Kotlov, Artur Baisangurov, Vladimir Shatsky, Daria Afenteva, Alexander Kuznetsov, Susan Raju Paul, Diane L Davies, Patrick M Reeves, Michael Lanuti, Michael F Goldberg, Cagdas Tazearslan, Madison Chasse, Iris Wang, Mary Abdou, Sharon M Aslanian, Samuel Andrewes, James J Hsieh, Akshaya Ramachandran, Yang Lyu, Ilia Galkin, Viktor Svekolkin, Leandro Cerchietti, Mark C Poznansky, Ravshan Ataullakhanov, Nathan Fowler, Alexander Bagaev
Journal: Cancer Cell (2022)
Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations
Authors: Paul K. Whelton, Robert M. Carey, Giuseppe Mancia, Reinhold Kreutz, Joshua D. Bundy, Bryan Williams
Journal: Circulation (2022)

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.
Removal of Small, Asymptomatic Kidney Stones and Incidence of Relapse
Authors: Mathew D. Sorensen, Jonathan D. Harper, Michael S. Borofsky, Tariq A. Hameed, Kimberly J. Smoot, Barbara H. Burke, Branda J. Levchak, James C. Williams, Michael R. Bailey, Ziyue Liu, James E. Lingeman
Journal: New England Journal of Medicine (2022)

The benefits of removing small (≤6 mm), asymptomatic kidney stones endoscopically is unknown. Current guidelines leave such decisions to the urologist and the patient. A prospective study involving older, nonendoscopic technology and some retrospective studies favor observation. However, published data indicate that about half of small renal stones left in place at the time that larger stones were removed caused other symptomatic events within 5 years after surgery.
Oscillatory positive expiratory pressure therapy in COPD (O-COPD): a randomised controlled trial
Authors: Saeed M Alghamdi, Abdullah S Alsulayyim, Ali M Alasmari, Keir E J Philip, Sara C Buttery, Winston A S Banya, Michael I Polkey, Surinder S Birring, Nicholas S Hopkinson
Journal: Thorax (2022)

Background Oscillatory positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance and reduce cough, but there is limited evidence for their effectiveness in COPD, or to guide patient selection. We aimed to assess the impact of OPEP therapy on quality of life and objective measures of cough and sleep disturbance in patients with COPD with regular sputum production. Methods We enrolled stable patients with COPD, who reported sputum production every day or most days, into an assessor-blind, parallel-group, randomised controlled trial comparing 3 months of using an Acapella device against usual care (including use of the active cycle of breathing technique). The primary outcome was cough-related quality of life measured using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included fatigue (Functional Assessment of Chronic Illness Therapy, FACIT score) and generic quality of life (EuroQol-5 Dimensions, EQ-5D). In a substudy (n=45), objective monitoring of cough and disturbance/movement during sleep were also available. Results 122 participants (61/61 OPEP/control) were recruited, 40% female, 17% smokers, FEV1 38 (25–56)% predicted, and age 62±10 years. 103 completed the study (55/48 OPEP/control). Use of OPEP was associated with an improvement in LCQ compared with controls; MD (95% CI) 1.03 (0.71 to 2.10); (p=0.03), FACIT score 4.68 (1.34 to 8.02); (p&lt;0.001) and EQ-5D 4.00 (0.49 to 19.75); (p=0.04). There was also an improvement in cough frequency −60 (−43 to −95) coughs/24 hours (p&lt;0.001), but no statistically significant effect on sleep disturbance was identified. Conclusions Regular use of an Acapella device improves symptoms and quality of life in people with COPD who produce sputum daily or most days. Trial registration number ISRCTN44651852 .
Enhanced rare disease mapping for phenome-wide genetic association in the UK Biobank
Authors: Matthew T. Patrick, Redina Bardhi, Wei Zhou, James T. Elder, Johann E. Gudjonsson, Lam C. Tsoi
Journal: Genome Medicine (2022)

Abstract Background Rare diseases collectively affect up to 10% of the population, but often lack effective treatment, and typically little is known about their pathophysiology. Major challenges include suboptimal phenotype mapping and limited statistical power. Population biobanks, such as the UK Biobank, recruit many individuals who can be affected by rare diseases; however, investigation into their utility for rare disease research remains limited. We hypothesized the UK Biobank can be used as a unique population assay for rare diseases in the general population. Methods We constructed a consensus mapping between ICD-10 codes and ORPHA codes for rare diseases, then identified individuals with each rare condition in the UK Biobank, and investigated their age at recruitment, sex bias, and comorbidity distributions. Using exome sequencing data from 167,246 individuals of European ancestry, we performed genetic association controlling for case/control imbalance (SAIGE) to identify potential rare pathogenic variants for each disease. Results Using our mapping approach, we identified and characterized 420 rare diseases affecting 23,575 individuals in the UK Biobank. Significant genetic associations included JAK2 V617F for immune thrombocytopenic purpura ( p = 1.24 × 10 −13 ) and a novel CALR loss of function variant for essential thrombocythemia ( p = 1.59 × 10 −13 ). We constructed an interactive resource highlighting demographic information ( http://www-personal.umich.edu/~mattpat/rareDiseases.html ) and demonstrate transferability by applying our mapping to a medical claims database. Conclusions Enhanced disease mapping and increased power from population biobanks can elucidate the demographics and genetic associations for rare diseases.
Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes
Authors: Iliana Soto, Mary Couvillion, Katja G. Hansen, Erik McShane, J. Conor Moran, Antoni Barrientos, L. Stirling Churchman
Journal: Genome biology (2022)

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA-encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we tailored ribosome profiling for the unique features of the human mitoribosome.